For Better or Worse: Older Dads Pass on More Mutations to Kids

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The older a father is, the more likely he will pass new mutations
to his children, upping the chances of disease, researchers say.

"A 36-year-old father gives twice more new mutations to his child
than a 20-year-old father does, and a 50-year-old father gives
about four times the number of mutations," said researcher Kari
Stefansson, chairman and CEO of deCODE Genetics in Reykjavik,
Iceland. "This is not a subtle effect — this is a very, very
large effect. And it increases the probability that a mutation
may strike a gene that is very important, which can lead to a
disease."

Genetic errors crop up in the body over time, and scientists had
conjectured that
older parents accumulate more mutations in their sperm and egg
cells than younger ones. To better understand the rate at which
novel mutations emerge over time, researchers sequenced the
entire genomes of 78 Icelandic trios of parents and offspring.

"Roughly 97.1 percent of the diversity in human mutation rates
appears due to the age of the father," Stefansson added. "There
is nothing else on the population level that impacts the level of
mutations in the human genome as much as the age of the father."
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On average, about two new mutations are added for every
additional year of a father's age at conception.

"If you compare a 40-year-old father with a 20-year-old father,
the 40-year-old is twice as likely to develop a child who
develops schizophrenia or autism," Stefansson said. "We know
there's been a fairly dramatic increase in the diagnosis of
autism in society — perhaps part of that may be accounted for by
the recent increase in age of fathers."

Still, although the researchers found that older fathers are at
greater risk than younger fathers of passing on new mutations,
"the absolute risk of older fathers conceiving a child that has a
life-threatening mutation or other mutation that affects them is
still relatively small," Stefansson cautioned.

In addition, although more mutations might seem damaging, and
often can be, the novelty that mutations generate in genomes is
a
major driver of evolution. "The more mutations we have in the
human genome, the more there is diversity for nature to select
from," Stefansson said.

Future studies can investigate whether these mutations are
randomly distributed across the genome or whether there are
hotspots within the genome for mutations. The scientists are also
interested in what percentage of disorders such as autism and
schizophrenia are due to new mutations versus inherited
mutations, Stefansson added.

Stefansson and his colleagues detailed their findings in the Aug.
23 issue of the journal Nature.